[Radiotheranostics Based on Chemical Control of Radioactivity Pharmacokinetics]

Recently, radiotheranostics, which systematically combines diagnosis by nuclear medicine imaging and treatment by internal radiotherapy, constitutes a new modality in cancer treatment, with some clinical reports showing marked effects on cancer. We have been developing multifunctional chelates containing a target recognition unit, a radiation release unit, and a radioactivity pharmacokinetics control unit in the same molecule to develop efficient agents for cancer radiotheranostics based on chemical control of radioactivity pharmacokinetics. Using these compounds, we have achieved improved cancer accumulation and reduced renal accumulation in tumor-bearing mice, and have developed novel hybrid radiotheranostic agents that can be applied to simultaneously perform target-specific molecular imaging using γ-ray emitting radionuclides and internal radiotherapy using α-particle-emitting radionuclides. For example, ¹¹¹In/²²⁵Ac-labeled PSMA-DA1, which targets prostate-specific membrane antigen (PSMA) for radiotheranostics, achieved clear in vivo imaging of PSMA in tumor-bearing mice and showed marked tumor growth inhibition. In addition to PSMA, this platform for radiotheranostics has also shown efficacy against various cancer target molecules, including carbonic anhydrase IX (CA-IX), which is highly expressed in hypoxic regions of cancer, and glucagon-like peptide-1 receptor (GLP-1R), which is highly expressed in insulinomas. This review presents these recent results of our studies on radiotheranostics for cancer.